Acute Cocaine Differentially Induces PKA Phosphorylation Substrates in Male and Female Rats

Introduction:

Cocaine use among women has steadily increased, rising to approximately 30% of users in the United States. As researchers pay more attention to hormonal effects on drug abuse, it is becoming apparent that men and women react differently to cocaine. Overall, women are more vulnerable to some aspects of cocaine abuse, such as being more sensitive to the addictive properties of cocaine, experiencing more nervousness after intermittentadministration of cocaine, taking longer to feel its subjective effects, reporting less euphoria, and having more severe cravings in response to cocaine-associated cues . Women also increase their rate of cocaine consumption more rapidly than do men, and once addicted it is more difficult for them to quit . Likewise, after abstinence, women use cocaine for longer periods than do men .

Similar to humans, female rodents also show exaggerated and more robust psychomotor responses to cocaine than do males . Females also more quickly develop cocaine-induced conditioned place preference (CPP) with lower doses and more readily acquire cocaine self-administration . Taken together, human and animal studies suggest that sex-specific differences exist at all stages of cocaine abuse including induction maintenance, and relapse.

Sex differences in the mesocorticolimbic dopamine (DA)system- -a regulator of cocaine’s psychomotor and rewarding effects have been demonstrated . As recently reviewed by Becker and Hu, there are sex differences in the levels of DA receptors in the striatum, in the efficacy of DA antagonists and agonists to block DA receptors, and in cocaine-induced accumbal DA release/reuptake. The sexually dimorphic pattern in DA system activation after cocaine treatment is postulated to be correlated with sex differences in cocaine-induced DA mediated intracellular responses.